scholarly journals AB0104 CORRELATION OF PLASMA 14-3-3Η LEVELS WITH DISEASE ACTIVITY MEASURES IN METHOTREXATE-NAÏVE RA PATIENTS TREATED WITH UPADACITINIB MONOTHERAPY IN THE SELECT-EARLY PHASE 3 STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1351.2-1351
Author(s):  
T. Sornasse ◽  
S. Chahal ◽  
Y. Gui ◽  
N. Nagarajan ◽  
A. Friedman ◽  
...  
Keyword(s):  
Disease Activity ◽  
Early Phase ◽  
Life Science ◽  
Joint Damage ◽  
Phase 3 ◽  
Radiographic Outcomes ◽  
Activity Measures ◽  
Clinical Measures ◽  
Over Time ◽  
Disease Activity Measures

Background:Early diagnosis and treat-to-target strategies in RA improve clinical and radiographic outcomes. 14-3-3η is a soluble diagnostic biomarker that is involved in the pathogenesis of RA (1) including the potent activation of key signalling cascades such as the JAK-STAT pathway and whose initial expression coincides with a transition to synovitis. In undifferentiated arthralgia, 14-3-3η independently predicts the development of RA. In confirmed RA, 14-3-3η levels decrease with treatment response (2) and those changes are associated with clinical and radiographic outcomes, including the prediction of joint damage progression in patients who have achieved clinical remission. Upadacitinib (UPA), an oral JAK1-selective inhibitor, demonstrated significant and clinically meaningful improvements in RA vs. methotrexate (MTX) in the SELECT-EARLY phase 3 study (3).Objectives:To determine the impact of treatment with UPA monotherapy 15 mg QD on the levels of plasma 14-3-3η and to explore its relationship with clinical measures in early MTX-naïve RA patients.Methods:Patients from the SELECT-EARLY study were randomly selected (UPA n = 100; MTX n = 100) from the pool of patients with available plasma samples. 14-3-3η tests were performed at Augurex according to standard operating procedures. Concentrations (ng/mL) were log-transformed for analysis. Non-parametric correlations between biomarker data and clinical end points were derived using the Spearman method. Changes in 14-3-3η over time were compared using a Repeated Measure Mixed Linear Model. All statistical analyses were conducted in JMP 14.1 (SAS Institute).Results:At baseline, 79% of patients were 14-3-3η positive (≥ 0.19 ng/mL) with similar levels in both arms. Baseline levels of 14-3-3η correlated significantly with baseline disease activity measures (CDAI ρ = 0.164, p = 0.042; DASCRP ρ = 0.222, p = 0.004; and SDAI ρ = 0.177, p = 0.028) but not with baseline mTSS (ρ =-0.021, p = 0.787); of note baseline mTSS were relatively low in this subset of early RA patients (median = 2, IQR [0 – 9.5]). Over time, 14-3-3η levels tended to be lower in both the UPA and MTX groups. However, only treatment with UPA for 24 weeks resulted in a significant decrease in circulating 14-3-3η (p = 0.0002) (Figure 1). In addition, at week 24 in the UPA arm, changes in 14-3-3η levels correlated significantly with changes in concurrent disease activity measures (Δ CDAI ρ = 0.264, p = 0.030; Δ DASCRP ρ = 0.267, p = 0.021; and Δ SDAI ρ = 0.267, p = 0.028) but not with change in mTSS (ρ =-0.186, p = 0.111). In contrast to UPA, the relatively small changes in 14-3-3η induced by MTX did not correlate with any clinical measures.Figure1Conclusion:This study demonstrates that treatment with UPA 15 mg QD monotherapy for 24 weeks significantly reduces the levels of circulating 14-3-3η in MTX-naïve RA patients and that these changes correlate with clinical measures of disease activity. Although we were not able to detect a clear relationship between changes in 14-3-3η and rate of structural damage progression, we would like to hypothesize that the superior clinical activity of UPA over MTX on joint damage may be related to the significant reduction in 14-3-3η induced by UPA; this hypothesis should be tested in a larger RA cohort with a larger proportion of joint damage progressors.References:[1]Maksymowych WP et al. Arthritis Res Ther. 2014;16(2):R99.[2]Hirata S et al. Arthritis Res Ther. 2015;17(1):280.[3]van Vollenhoven R et al. Arthritis Rheumatol.;2018 (Suppl 10; vol.70).Disclosure of Interests:Thierry Sornasse Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Simran Chahal Shareholder of: Augurex Life Science Corp, Employee of: Augurex Life Science Corp, Yuan Gui Shareholder of: Augurex Life Science Corp, Employee of: Augurex Life Science Corp, Neeraja Nagarajan Employee of: Augurex Life Science Corp, Alan Friedman Shareholder of: AbbVie Inc, Employee of: AbbVie Inc, Norma Biln Shareholder of: Augurex Life Science Corp, AbbVie Inc, Employee of: Augurex Life Science Corp

scholarly journals Synovitis in rheumatoid arthritis detected by grey scale ultrasound predicts the development of erosions over the next three years

Rheumatology ◽  
2019 ◽  
Vol 59 (7) ◽  
pp. 1556-1565 ◽  
Author(s):  
Burkhard Möller ◽  
Daniel Aletaha ◽  
Michael Andor ◽  
Andrew Atkinson ◽  
Bérengère Aubry-Rozier ◽  
...  
Keyword(s):  
Disease Activity ◽  
Joint Damage ◽  
Clinical Disease ◽  
Biological Dmards ◽  
Clinical Disease Activity ◽  
Upper Limit ◽  
Grey Scale ◽  
Damage Progression ◽  
Activity Measures ◽  
Disease Activity Measures

Abstract Objectives To evaluate grey scale US (GSUS) and power Doppler US synovitis (PDUS), separately or in combination (CombUS), to predict joint damage progression in RA. Methods In this cohort study nested in the Swiss RA register, all patients with sequential hand radiographs at their first US assessment were included. We analysed the summations of semi-quantitative GSUS, PDUS and CombUS assessments of both wrists and 16 finger joints (maximum 54 points) at their upper limit of normal, their 50th, 75th or 87.5th percentiles for the progression of joint damage (ΔXray). We adjusted for clinical disease activity measures at baseline, the use of biological DMARDs and other confounders. Results After a median of 35 months, 69 of 250 patients with CombUS (28%), 73 of 259 patients with PDUS (28%) and 75 of 287 patients with available GSUS data (26%) demonstrated joint damage progression. PDUS beyond upper limit of normal (1/54), GSUS and CombUS each at their 50th (9/54 and 10/54) and their 75th percentiles (14/54 and 15/54) were significantly associated with ΔXray in crude and adjusted models. In subgroup analyses, GSUS beyond 14/54 and CombUS higher than 15/54 remained significantly associated with ΔXray in patients on biological DMARDs, while clinical disease activity measures had no significant prognostic power in this subgroup. Conclusion Higher levels of GSUS and CombUS are associated with the development of erosions. GSUS appears to be an essential component of synovitis assessment and an independent predictor of joint damage progression in patients on biological DMARDs.

scholarly journals THU0207 SUSTAINABILITY OF RESPONSE TO UPADACITINIB AS MONOTHERAPY OR IN COMBINATION AMONG PATIENTS WITH RHEUMATOID ARTHRITIS AND PRIOR INADEQUATE RESPONSE TO CONVENTIONAL SYNTHETIC DMARDS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 327.1-328
Author(s):  
A. Kavanaugh ◽  
M. H. Buch ◽  
B. Combe ◽  
L. Bessette ◽  
I. H. Song ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inadequate Response ◽  
Research Support ◽  
Two Phase ◽  
First Occurrence ◽  
Activity Measures ◽  
Disease Activity Measures

Background:The primary treatment goal for patients (pts) with rheumatoid arthritis (RA) is a state of sustained clinical remission (REM) or low disease activity (LDA).1,2Objectives:To assess the long-term sustainability of responses to upadacitinib (UPA), a JAK inhibitor, with or without background csDMARD(s) in pts with RA.Methods:Data are from two phase 3 randomized, controlled trials of UPA in RA pts with roughly similar baseline disease characteristics: SELECT-NEXT enrolled pts with an inadequate response (IR) to csDMARD(s) on background stable csDMARD(s) receiving UPA 15 mg or 30 mg once daily or placebo for 12 weeks (wks); SELECT-MONOTHERAPY enrolled methotrexate (MTX)-IR pts receiving UPA 15 mg or 30 mg monotherapy or blinded MTX for 14 wks. After 12/14 wks, pts could enter a blinded long-term extension and receive UPA 15 mg or 30 mg for up to 5 years. This post hoc analysis evaluated clinical REM (CDAI ≤2.8; SDAI ≤3.3), LDA (CDAI≤10; SDAI≤11), and DAS28(CRP) <2.6/≤3.2 at first occurrence before Wk 84; additionally, these measures were evaluated at 3, 6, and 12 months after the first occurrence for the total number of pts randomized to UPA 15 mg. Sustainability of response was evaluated by Kaplan-Meier only for those pts who achieved REM/LDA and was defined as time to the earliest date of losing response at two consecutive visits or discontinuation of study drug. The predictive ability of time to clinical REM/LDA was assessed using Harrell’s concordance (c)-index (for reference, an index ~ 0.5, indicates no ability to predict; an index of 1 or -1 would be a perfect prediction). The last follow up dates were 22 March, 2018 (SELECT-NEXT) and 25 May, 2019 (SELECT-MONOTHERAPY), when all pts had reached the Wk 84 visit.Results:Through Wk 84, the percent of treated pts achieving CDAI REM/LDA was 43%/79% for those receiving UPA 15 mg with background csDMARD(s) (SELECT-NEXT) and 37%/76% for those receiving UPA 15 mg without background csDMARD(s) (SELECT-MONOTHERAPY). 35%/25% of pts randomized to UPA 15 mg with background csDMARD(s) and 27%/23% of pts randomized to UPA 15 mg without background csDMARD(s) achieved sustained CDAI REM through 6/12 months after the first occurrence. 64%/56% of pts randomized to UPA 15 mg with background csDMARD(s) and 61%/56% of pts randomized to UPA 15 mg without background csDMARD(s) achieved sustained CDAI LDA through 6/12 months after the first occurrence (Figure 1). Time to initial clinical REM/LDA did not appear to be associated with sustained disease control. The c-indices (95%CI) for CDAI REM in the UPA 15 mg with background csDMARD(s) and UPA 15 mg without background csDMARD(s) groups were 0.541 (0.47, 0.62) and 0.568 (0.49, 0.65) and that of LDA were 0.521 (0.46, 0.58) and 0.498 (0.43, 0.56), respectively. Through last follow-up visit, 55% of pts receiving UPA 15 mg with background csDMARD(s) and 62% of pts receiving UPA 15 mg without background csDMARD(s) remained in CDAI REM while 72% and 70% of pts remained in CDAI LDA, respectively (Figure 2). Similar results were observed across other disease activity measures (SDAI REM/LDA and DAS28(CRP) <2.6/≤3.2).Conclusion:More than a quarter and more than a half of pts with RA and prior IR to csDMARD(s) receiving UPA with or without background csDMARD therapy achieved sustained clinical REM and LDA, respectively, across disease activity measures. Sustainability of responses appeared comparable among pts receiving UPA with or without background csDMARDs through up to 84 wks.References:[1]EULAR: Smolen JS, et al. Ann Rheum Dis 2017;76:960–977.[2]ACR: Singh et al. Arthritis & Rheumatology Vol. 68, No. 1, January 2016, pp 1–26.Disclosure of Interests: :Arthur Kavanaugh Grant/research support from: Abbott, Amgen, AstraZeneca, BMS, Celgene Corporation, Centocor-Janssen, Pfizer, Roche, UCB – grant/research support, Maya H Buch Grant/research support from: Pfizer, Roche, and UCB, Consultant of: Pfizer; AbbVie; Eli Lilly; Gilead Sciences, Inc.; Merck-Serono; Sandoz; and Sanofi, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp & Dohme; Pfizer; Roche-Chugai; UCB, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, In-Ho Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Yanna Song Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Jessica Suboticki Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Peter Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, Roche, Sanofi, UCB

scholarly journals Measures of Rheumatoid Arthritis Disease Activity in Australian Clinical Practice

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Andrew Taylor ◽  
Hanish Bagga
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Disease Activity ◽  
Disease Process ◽  
Biological Agent ◽  
Rheumatoid Arthritis Disease Activity ◽  
Retrospective Audit ◽  
Rheumatoid Arthritis Disease ◽  
Activity Measures ◽  
Disease Activity Measures

Objectives. To investigate which rheumatoid arthritis (RA) disease activity measures are being collected in patients receiving glucocorticoids, non-biologic or biologic disease-modifying antirheumatic drugs (DMARDs) in Australian rheumatology practice. Methods. A retrospective audit of medical records was conducted from eight rheumatology practices around Australia. Each rheumatologist recruited 30 consecutive eligible patients into the review, 10 of whom must have been receiving a biological agent for rheumatoid arthritis. Disease activity measures and radiographic assessments were collected from each patient's last consultation. For biologic patients, disease activity measures were also collected from when the patient was first initiated on the biological agent. Results. At last consultation, the disease measures that were recorded most often were ESR (89.2%), haemoglobin (87.5%), and CRP (84.2%). DAS28 was infrequently recorded (16.3%). The rate of recording disease activity measures for patients receiving biologic DMARDs decreased over time (mean 27 months). Conclusion. This review has shown inconsistency of RA activity measures being recorded in Australian rheumatology clinical practice. An accurate assessment of the disease process is necessary to effectively target rheumatoid arthritis patients to treat in order to achieve optimal outcomes.

scholarly journals POS1067 BASELINE VITAMIN D LEVELS AND DISEASE ACTIVITY AND RESPONSE IN PORTUGUESE PATIENTS WITH PSORIATIC ARTHRITIS UNDER bMDARD: DOES IT MAKE A DIFFERENCE?

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 812.1-812
Author(s):  
F. Oliveira Pinheiro ◽  
B. M. Fernandes ◽  
S. Garcia ◽  
M. Rato ◽  
D. Fonseca ◽  
...  
Keyword(s):  
Vitamin D ◽  
Psoriatic Arthritis ◽  
Disease Activity ◽  
Rheumatic Diseases ◽  
Response To Therapy ◽  
Response Criteria ◽  
National Database ◽  
Vitamin D Levels ◽  
Activity Measures ◽  
Disease Activity Measures

Background:There is growing evidence that vitamin D [25(OH)D]) plays an important role in maintaining skeletal health and modulating the immune system. Epidemiological data indicate that vitamin D deficiency is common in immune-mediated rheumatic diseases, especially in rheumatoid arthritis, but there is little data regarding its association with disease activity and response to therapy in patients with psoriatic arthritis (PsA) under bDMARD therapy.Objectives:We aimed to assess whether 25(OH)D basal levels correlate with disease activity and clinical response to the first bDMARD, at 6 and 12 months of therapy, in a monocentric cohort of patients with PsA.Methods:This retrospective study was carried out on PsA patients from a Rheumatology department of a tertiary hospital, fulfilling CASPAR criteria and registered in our national database (Reuma.pt), who started the first bDMARD since 2008. Demographic, clinical and laboratory criteria were evaluated at 0, 6 and 12 months of biologic therapy. Disease activity was assessed using CDAI, SDAI, DAS28(4V), BASDAI, ASDAS, DAPSA and the response was measured using the EULAR, BASDAI50, ASDAS, ASAS, ACR and PsARC responses. Correlations were made between absolute serum levels of 25(OH)D and continuous variables, as well as associations between different vitamin D cutoffs and disease activity measures and response criteria. Multiple linear and logistic regression analyses were performed to determine whether vitamin D is a predictor of disease activity and therapeutic response.Results:We included 81 patients, 41 (50.6%) females; with a mean age of 48.0±11.7 years, a mean disease duration of 9.5±7.4 years and a mean body mass index of 28.4±5.2 kg/m2. Thirteen (16.0%) were smokers. The mean 25(OH)D basal level was 25.5±13.2 ng/ml, 21 (25.9%) had 25(OH)D basal levels ≥30 ng/mL and 31 (38.3%) ≤20 ng/mL. Sixty-two patients (76.5%) were under csDMARD therapy. Golimumab (29, 35,8%), etanercept (28, 34.6%) and adalimumab (10, 12.3%) were the most frequently prescribed bDMARDs. There were only very weak, albeit positive, correlations between 25(OH)D levels and measures of disease activity. The BASDAI50 response at 6 months was associated with higher basal 25(OH)D levels (29.5±14.5 vs 21.5±10.2 ng/mL, p = 0.013); the ASAS20 (33.9±15.9 vs 24.2±12.8 ng/mL; p = 0.023), ASAS40 (31.9±14.6 vs 25.0±13.8 ng/mL; p = 0.023) and ASAS70 (47.0±4.2 vs 26.6±14.2; p = 0.027) responses at 12 months were associated with higher basal levels of 25(OH)D; basal 25(OH)D levels were ≥ 30ng/mL in a significantly higher proportion of patients who achieved CDAI (38.9% vs 10.5%; p = 0.027) and SDAI (38.9% vs 7.7%; p = 0.008) remission and ASDAS disease inactive (29.4% vs 7.3%; p = 0.040) at 1 year. In the regression models, basal levels of 25(OH)D were found to be predictors of good EULAR responders (OR 1.315, 1.017-1.213 95% CI; p = 0.037) at 6 months. Basal levels of 25(OH)D were not significantly different in patients who discontinued bDMARD and no significant correlations or associations were identified regarding more specific PsA activity measures, such as DAPSA and PsARC, nor were they predictive of these responses.Conclusion:We can conclude that there is a global trend for an association between higher levels of vitamin D and lower measures of disease activity and better therapeutic responses to the first biologic. It was possible to find statistically significant associations with some disease activity measures and response criteria that, although primarily designed for other rheumatic diseases, are often used in PsA.Disclosure of Interests:None declared.

SAT0046 MODIFIED DISEASE ACTIVITY SCORE AT 3 MONTHS IS A SIGNIFICANT PREDICTOR FOR RAPID RADIOGRAPHIC PROGRESSION AT 12 MONTHS COMPARED WITH OTHER MEASURES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 954.1-954
Author(s):  
M. Movahedi ◽  
D. Weber ◽  
P. Akhavan ◽  
E. Keystone
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Radiographic Progression ◽  
Activity Score ◽  
Controlled Study ◽  
Tender Joint Count ◽  
Double Blind ◽  
Activity Measures ◽  
Disease Activity Measures

Background:Progressive rheumatoid arthritis (RA) is responsible for joint damage causing disabilities with no agreement on which disease measures best predict radiographic progressionObjectives:We aimed to determine which disease activity measures including disease activity score (DAS), modified (M) DAS28 (CRP), clinical disease activity index (CDAI), and health assessment questionnaire disability index (HAQ-DI) best predict rapid radiographic progression (RRP) in early RA patients at baseline (BL) and 3 months.Methods:PREMIER data, a 2-year, multicenter, double-blind active comparator–controlled study with methotrexate (MTX) naïve RA patients and active disease <3 years, were used. Only patients in the MTX arm were analyzed. RRP was defined as change in modified total Sharp (mTSS) > 3.5 at month 12. Logistic regression analysis assessed impact of measures at BL and 3 months on RRP at 12 months. Best cut-off points of M-DAS28(CRP) was also estimated using area under the receiver operating characteristic curve.Results:149 patients were included: female (n=113; 75.8%), positive RF (n=127; 85.2%), mean (SD) age 52.9 (13.3) years, disease duration 0.8 (0.9) year, DAS28(CRP) 6.3 (0.9). After adjusting for potential confounders, only M-DAS28(CRP) at BL (adjOR=3.29; 95% CI: 1.70-6.36) and 3 months (adjOR=2.56; 95% CI: 1.43-4.56) strongly predicted RRP at 12 months. M-DAS28(CRP) 4.5 and 2.6 at BL and 3 months maximized sensitivity and specificity for prediction of RRP.Conclusion:M-DAS28(CRP) was a stronger predictor at BL and 3 months for RRP compared with other disease activity measures. Removing tender joint count and patient global assessment from DAS28(CRP) improves prediction of RRP.References:[1] Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis and rheumatism. 2006;54(1):26-37.Acknowledgments :The authors wish to knowledge AbbVie Canada Inc. for providing patients data.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Deborah Weber: None declared, Pooneh Akhavan: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB

Do Radiographic Joint Damage and Disease Activity Influence Functional Disability Through Different Mechanisms? Direct and Indirect Effects of Disease Activity in Established Rheumatoid Arthritis

2013 ◽  
Vol 40 (9) ◽  
pp. 1505-1512 ◽  
Author(s):  
Sandhya C. Nair ◽  
Johannes W.J. Bijlsma ◽  
Jacobien H. van der Werf ◽  
Maaike J. van der Veen ◽  
Suzanne P. Linn-Rasker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Functional Decline ◽  
Joint Damage ◽  
Treatment Strategies ◽  
Joint Disease ◽  
Influence Functional ◽  
Over Time ◽  
Predictive Effect

Objective.To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy.Methods.Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28.Results.In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28.Conclusion.In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.

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